tbuckley/cabot-search huggingface dataset:
Assessing the interrelation between oestrogen receptor status, heart rate variability and serum nitric oxide in breast cancer patients: Understanding their prognostic relevance.
Authors: Madhuri Taranikanti, Aswin Kumar Mudunuru, Akhila Dronamraju, Rohith Kumar Guntuka, Aruna Kumari Yerra, Srinivas Maddur, Lasya Manchikanti, Sai Shriya Taranikanti
Journal: Journal of Clinical Oncology (2022)

e12564 Background: Heart Rate Variability (HRV) is a non-invasive procedure to assess cardiac functions and provides an index of autonomic function that intricately controls vascular tone. Studying the alteration in HRV with agents producing oxidative stress will provide useful information about disease progression. Lower HRV indicates low level of Parasympathetic Nervous System activation and dysregulation of cardiac functions. Elements of tumour microenvironment like prostaglandin E2, oestrogen and hypoxia stimulate nitric oxide (NO) production which reacts with free radicals released by tumour tissue forming oxidising agents. NO enhances oxidative stress causing vascular dysfunction. Very few studies have reported an interrelationship between NO and HRV parameters in breast cancer. The aim of the study is to verify the relation between HRV and serum NO levels in ER+ and ER- breast cancer groups. Methods: Study design: Analytical, Cross sectional. Sample Size: 135 women above 20 years of age with and without breast cancer. 69 women with histologically proven breast cancer in different stages and 66 women who were healthy age matched controls were included. Oestrogen Receptor (ER) status was obtained from clinical records. Out of 69 women with breast cancer, 31 were ER- with 15 in stage 1 and 16 in stage 2. 38 women were ER+ with 5 in stage 2 and 33 in stage 3. Serum NO was measured using colorimetry. Heart Rate Variability was measured from lead II ECG using Power Lab 15T and lab chart software. Serum NO levels and HRV parameters were compared between ER groups. Results: ER+ women had higher HRV with parasympathetic predominance compared to ER- with p&lt;0.001. ER+ women also had higher serum NO levels compared to ER- group with p&lt;0.001. Though no direct correlation was noticed between NO and HRV, multiple analysis of variance showed significant (p&lt;0.001) difference of all values across the groups. irrespective of menopausal status. Conclusions: A significant difference was observed in HRV of ER+ and ER- women with breast cancer. Most ER+ women were in stage 3 with significantly higher NO levels. Serum NO is expected to be the factor most responsible for HRV changes particularly in stage 3/ER+. Parasympathetic predominance seen in ER+ women possibly is due to high NO levels.[Table: see text]
Intravesical botulinum toxin use in detrusor overactivity: A comparison of long-term outcomes in patients with Multiple Sclerosis and Idiopathic Detrusor Overactivity
Authors: J. Kealey, G. Chan, H. Yao, H. O'Connell, J. Gani, R. Parkinson, A. Bazo
Journal: European Urology (2022)
The ethnomedicinal and functional uses, phytochemical and pharmacology of compounds from <i>Ardisia</i> species: An updated review
Authors: Bingrui Liu, Rongyu Liu, Qifeng Liu, Charles R. Ashby, Hang Zhang, Zhe‐Sheng Chen
Journal: Medicinal Research Reviews (2022)

Abstract Medicinal plants are considered to be a critical source of novel compounds and pharmacophores. The genus Ardisia , consisting of approximately 500 species, is the largest genus in the Myrsinaceae family. Ardisia species are widely distributed throughout tropical and subtropical regions of the world and have been used for the treatment of cancer, hypertension, irregular menstruation, gonorrhea, diarrhea and postnatal syndromes, among others. Phytochemical studies of Ardisia species have resulted in the isolation and identification of 111 compounds, including triterpenoid saponins, quinones, phenols, coumarins, cyclic depsipepetide and flavonoids. Crude extracts and isolates from Ardisia have been reported to have in vitro and in vivo efficacies, including but not limited to anticancer, antiinflammatory, antimicrobial, antioxidant, antithrombotic and antidiabetic, antitubercular compounds. This review focuses on the medical and functional uses, phytochemical profile and pharmacological efficacies of Ardisia species over the past 15 years. This review will provide information indicating that Ardisia species represent an invaluable source of potential therapeutic compounds.
Asia subpopulation analysis from the phase III POLARIX trial.
Authors: Yuqin Song, Jie Jin, Herve Tilly, Huilai Zhang, Junning Cao, Jifeng Feng, Liling Zhang, Shinya Rai, Hideki Goto, Yasuhito Terui, Won Seog Kim, Ho-Jin Shin, Jyh-Pyng Gau, Cheng-Hong Tsai, Jeff Porter Sharman, Lilian Bu, Jamie Hirata, Calvin Lee, Koji Izutsu, Jun Zhu
Journal: Journal of Clinical Oncology (2022)

7558 Background: In the pivotal Phase III POLARIX trial, Pola-R-CHP demonstrated significantly improved progression-free survival (PFS) compared with R-CHOP, with a similar safety profile in patients with previously untreated DLBCL (Tilly et al. 2022). An Asia subpopulation analysis was included as part of the trial design; patients enrolled in Asia were analyzed for the purpose of registration in China of POLARIX (NCT03274492). Methods: Patients from mainland China, Hong Kong, Japan, South Korea, and Taiwan (enrolled during the global phase), and from the China extension cohort were included in the Asia subpopulation. POLARIX methods were previously described (Tilly et al. 2022). Briefly, patients with untreated DLBCL were randomized 1:1 using the same stratification factors to receive six cycles of Pola-R-CHP or R-CHOP, plus two cycles of rituximab alone. The purpose of this analysis was to evaluate consistency of PFS (defined as ≥50% risk reduction in PFS) in the Asia subpopulation with the global population. Results: Overall, 281 patients (intent-to-treat population; 150, 85, 31 and 15 patients in mainland China, Japan, South Korea and Taiwan, respectively) were analyzed (141 received Pola-R-CHP and 140 received R-CHOP); 160 patients from the global population and 121 from the China extension cohort. Median age was 63 (range 19–79) years, and most patients had an International Prognostic Index of 3–5 (61.9%). At the data cut-off of June 28, 2021, (median follow-up of 24.2 months) PFS was superior with Pola-R-CHP vs R-CHOP (hazard ratio [HR] 0.64; 95% confidence interval [CI]: 0.40–1.03) and met the consistency definition with the global population. The 2-year PFS rate was 74.2% (95% CI: 65.7–82.7) with Pola-R-CHP vs 66.5% (95% CI: 57.3–75.6) with R-CHOP. Other key efficacy results were similar to the global study results (Table). The safety profile was generally comparable for Pola-R-CHP vs R-CHOP, including rates of grade 3–4 adverse events (AEs; 72.9% vs 66.2%), serious AEs (32.9% vs 32.4%), grade 5 AEs (1.4% vs 0.7%), AEs leading to discontinuation of any study treatment (5.0% vs 7.2%), and incidence of peripheral neuropathy (all grades, 44.3% vs 50.4%), respectively. Key efficacy results. CR, complete response. Conclusions: The results from the Asia subpopulation of POLARIX were consistent with the global study, with a clinically meaningful improvement in PFS (risk of disease progression, relapse or death reduced by 36%) following treatment with Pola-R-CHP vs R-CHOP, and a comparable safety profile in Asian patients with previously untreated DLBCL. Clinical trial information: NCT03274492. [Table: see text]
Acquired EGFR-resistant mutations in non–small cell lung cancer (NSCLC).
Authors: Luis E. Raez, Yasmine Baca, Jorge J. Nieva, Hirva Mamdani, Gilberto Lopes, Hossein Borghaei, Mark A. Socinski, Chadi Nabhan, Antoinette J. Wozniak, Ari M. Vanderwalde, Carlos Carracedo Uribe, Hina Khan, Stephen V. Liu, Misako Nagasaka
Journal: Journal of Clinical Oncology (2022)

9113 Background: EGFR mutations are present in more than 10% of patients (pts) with NSCLC in the US. While EGFR with tyrosine kinase inhibitors (TKIs) are effective, acquired resistance is expected. Known mechanisms include acquired EGFR mutations (e.g. 718V, c797x, 724s, 721s or T790M); copy number amplifications in MET, ERBB2, and PIK3CA; gene fusion events; and histological transformation. We herein present the prevalence of resistance mutations in the largest reported cohort of EGFR mutant NSCLC. Methods: Non-small cell lung cancer (NSCLC) tumor samples were submitted to Caris Life Sciences (Phoenix, AZ) for NextGen Sequencing (NextSeq, 592 Genes) and whole exome sequencing (NovaSeq, WES). PD-L1 expression was tested by IHC using 22c3 (Dako) and TPS scores were reported (cutoff &gt;1). TMB was measured by totaling somatic mutations (TMB-high cut-off &gt; 10 mutations per MB), genomic loss of heterozygosity (gLOH) was determined by WES. Patient treatment information was obtained from insurance claims data. Results: A total of 27,848 NSCLC tumors were evaluated and 3,223 (12%) had a EGFR sensitizing mutations. We found 60 tumors with common missense resistance mutations: 790 (n = 30, 0.9%), 797 (n = 38, 1.2 %), 718 (n = 11, 0.3%), 724 (n = 7, 0.2%) and 721 (n = 4, 0.1). Table 1 describes the frequencies, PD-L1 expression and the most common co-mutations. TMB-H (&gt; = 10) was found in 12.5% of the tumors and dMMR/MSI-H in 1.8%. The most prevalent co-alterations were TP53 54%), gLOH (28%), CTNNB1 (19%), NFKB1A (13%), APC (10%), PIK3CA (11%), SMAD4 (9%) and other 15 co-mutations in less than 7% were seen. In the 30 T790M mutants, in addition to TP53 mutations, other prevalent co-mutations were PIK3CA (14%) and CTNNB1 (17%). In 797-mutant tumors, in addition to T790M, the most prevalent co-mutations were TP53 (53%), CTNNB1 (22%), APC (16%) and PIK3CA (11%). L718 mutations co-occurred with either L858R (8/11), exon 19 (3/11) or T790M mutations (3/11). G724 mutations were found in 7 patients (0.02%) and G721 mutations in 4 patients (0.01%). Conclusions: Acquired resistance in EGFR mutant NSCLC is very heterogeneous and their frequency is still low most likely due to lack of enough sequencing of EGFR resistant tumors. While T790M and C797S mutations are well described, this report also notes a significant number of L718V mutations, primarily in osimertinib-treated pts with an original L858R. These data support the NGS evaluation of patients with resistant EGFR mutant lung cancers. [Table: see text]
Cancer stem cell assay for identification of effective treatments for platinum-resistant recurrent ovarian cancer.
Authors: Pier Paolo Claudio, Candace M. Howard, Anisha P Valluri, Logan Lawrence, Stephen Bush, Nadim Bou Zgheib, Seth T. Lirette, Krista L Denning, Jagan Valluri
Journal: Journal of Clinical Oncology (2022)

e17584 Background: Disease recurrence and progression of ovarian cancer is a common event, which is accompanied by the development of platinum-resistant or refractory disease. The presence of chemo-resistant cancer stem cells (CSCs) contributes to tumor propagation, maintenance, and treatment resistance of this difficult to treat disease. The choice of appropriate chemotherapy is critical to the management of advanced epithelial ovarian cancer. We developed a CSCs assay (ChemoID) that identifies the most effective chemotherapy for individual patients from a panel of FDA-approved chemotherapies. Methods: Ascites or interventional radiology biopsies were collected under physician order from 85 consecutive patients affected by 3rd relapsed ovarian cancer. Test results from the assay were used to treat patients with the highest cell kill drugs, taking into consideration their health status and using dose reductions, if needed. Our study assessed the correlation of the ChemoID test results to treatment outcomes independently of other biomarkers. A retrospective chart analysis and review of CT and PET scans were performed to determine patients’ outcomes for tumor response, progression-free survival (PFS), and overall survival (OS). Results: We observed that recurrent ovarian cancer patients treated with high-cell kill chemotherapy agents guided by the ChemoID drug response assay had an improvement in their median PFS and OS when compared to historical median PFS and OS and/or when compared to patients who could not receive high cell kill chemotherapies (PFS low cell kill 3.5 months vs. high cell kill 12.0 months; OS low cell kill 6.0 months vs. high cell kill 15.0 months). Conclusions: The current evidence strongly suggests that the ChemoID assay predicted the effectiveness of specific therapies, as well as improved outcomes for patients treated with assay-sensitive therapies.
Peptide‐Based Cancer Vaccine Delivery via the STINGΔTM‐cGAMP Complex
Authors: Yanpu He, Celestine Hong, Samantha J. Fletcher, Adam G. Berger, Xin Sun, Mengdi Yang, Shengnan Huang, Angela M. Belcher, Darrell J. Irvine, Jiahe Li, Paula T. Hammond
Journal: Advanced Healthcare Materials (2022)

With the advent of bioinformatic tools in efficiently predicting neo-antigens, peptide vaccines have gained tremendous attention in cancer immunotherapy. However, the delivery of peptide vaccines remains a major challenge, primarily due to ineffective transport to lymph nodes and low immunogenicity. Here, a strategy for peptide vaccine delivery is reported by first fusing the peptide to the cytosolic domain of the stimulator of interferon genes protein (STINGΔTM), then complexing the peptide-STINGΔTM protein with STING agonist 2'3' cyclic guanosine monophosphate-adenosine monophosphate (cGAMP). The process results in the formation of self-assembled cGAMP-peptide-STINGΔTM tetramers, which enables efficient lymphatic trafficking of the peptide. Moreover, the cGAMP-STINGΔTM complex acts not only as a protein carrier for the peptide, but also as a potent adjuvant capable of triggering STING signaling independent of endogenous STING protein-an especially important attribute considering that certain cancer cells epigenetically silence their endogenous STING expression. With model antigen SIINFEKL, it is demonstrated that the platform elicits effective STING signaling in vitro, draining lymph node targeting in vivo, effective T cell priming in vivo as well as antitumoral immune response in a mouse colon carcinoma model, providing a versatile solution to the challenges faced in peptide vaccine delivery.
Association between area deprivation index and quality of life and psychosocial well-being following breast cancer surgery.
Authors: Abbas Hassan, Huan T Nguyen, Joseph P Corkum, Jun Liu, Sahil K Kapur, Carrie K. Chu, Charles E. Butler, Anaeze Chidiebele Offodile
Journal: Journal of Clinical Oncology (2022)

e18612 Background: Neighborhood-level factors have been shown to influence surgical outcomes through material deprivation, psychosocial mechanisms, health behaviors, and access to resources. To date, no study has been conducted to examine the relationship between area-level deprivation (ADI) and post-mastectomy outcomes. Methods: We conducted a cross-sectional survey of all adult female breast cancer patients who underwent lumpectomy or mastectomy between January 2018 to June 2019. Patient-specific demographics, clinical history and ADI information were abstracted and correlated with post-operative global- (SF-12) and condition-specific (Breast-Q) quality-of-life performance via multivariable regression. Patients were classified into three groups based on their ADI scores: 0–39 (prosperous/comfortable), 40–59 (mid-tier), and 60–100 (at risk/distressed). Results: A total of 564 consecutive patients were identified; mostly white (75%) with a mean age of 60.2±12.4, mean body mass index (BMI) of 28.8±7.1, mean Charlson Comorbidity Index of 3.5±2.0, and mean ADI of 42.3±25.7. Minority patients and those with high BMI were more likely to reside in highly-deprived neighborhoods (p = 0.003 and p &lt; 0.001). In adjusted models, Patients at risk/distressed had significantly lower mean SF-12 physical (44.9 [95%CI, 43.8-46.0] vs. 44.9 [95%CI, 43.7-46.1] vs. 46.3 [95%CI, 45.3-47.3], p = 0.03) and BREAST-Q psychosocial well-being scores (63.5 [95%CI, 59.32-67.8] vs. 69.3 [95%CI, 65.1-73.6] vs. 69.7 [95%CI, 66.4-73.1], p = 0.01) than the mid-tier and prosperous/comfortable groups. Conclusions: Patients residing in deprived neighborhoods were more likely to have worse psychological well-being and quality of life. ADI should be incorporated in the shared-decision making process and perioperative counselling to engender value-based and personalized care, especially for vulnerable populations.
Clinical and economic outcomes associated with upfront comprehensive genomic profiling in newly diagnosed advanced lung cancer in the United States from 2018-2020: Evidence from the SEQUENCE study.
Authors: Gboyega Adeboyeje, Eleanor Caplan, Yihua Xu, Monica Chase, Nicole Myer, Sheetal Sheth, Brandon T Suehs
Journal: Journal of Clinical Oncology (2022)

9126 Background: As the number of approved molecularly-targeted therapies for the treatment of lung cancer increases, the debate continues as to whether a clinical strategy leveraging next-generation sequencing (NGS) comprehensive genomic profiling (CGP) to match patients to targeted treatments is advantageous versus a narrow/single-gene (N/S) panel testing. We examined clinical and economic outcomes of patients with advanced lung cancer (aLC) in the United States (US). Methods: In this retrospective study, newly diagnosed aLC patients aged 65-89 years were identified from a US Medicare Advantage plan from 2018-2020. Patients receiving genomic testing within 90 days of diagnosis and an FDA-approved pharmacotherapy cancer treatment after diagnosis were categorized by initial sequencing with NGS CGP (51+ genes) vs N/S (≤50 genes) panel testing using administrative claims based on previously validated algorithms. We assessed the proportion of patients with an inpatient or emergency department (INP/ED) visit for select outcomes (e.g., neutropenia) within 6 months of start of treatment, all-cause mortality, and PPPM (per patient per month) total healthcare costs through all available follow-up. Genomic testing costs within 90 days of cancer diagnosis were estimated using the Medicare fee schedule. Among patients with treatment within 30 days of testing, we assessed the proportion who did not switch treatment and were alive within 6 months. Descriptive analyses were conducted, and average effects were estimated using inverse probability weighted regression models. Results: We identified 3,532 patients who received genomic testing and pharmacotherapy cancer treatment (NGS CGP, n = 968; N/S, n = 2,564). Characteristics were similar between testing groups. The proportion of patients with INP/ED for outcomes of interest was similar following NGS CGP vs. N/S panels (15.0% vs. 17.8%; IRR [95% CI]: 0.76 [0.57 – 1.02]; p = 0.066), as were mortality (56.2% vs. 59.2%; HR: 1.05 [0.95 - 1.16]; p = 0.323) and PPPM costs (PPPM median cost difference -$575; ratio from regression 0.99, 0.94-1.04; p = 0.228). Among a subgroup of patients treated within 30 days of testing, a higher proportion receiving NGS CGP did not switch treatment and were alive after 6 months (47.6%) vs those receiving N/S panels (39.8%) (OR [95% CI]: 1.33 [1.12 - 1.59]; p = 0.001). Median genomic testing costs were $3,049 for NGS CGP vs. $218 for N/S testing. Conclusions: Outcomes were similar between patients receiving NGS CGP and N/S panel testing. Among patients with treatment within 30 days of testing, upfront NGS CGP was associated with fewer patients switching treatment and 6-month survival. Upfront testing with NGS CGP may represent a beneficial genomic profiling strategy as part of the initial management of patients with aLC.
OTHR-40. DICER 1- a rare , but important tumor driver in malignant progressive brain tumors
Authors: Iris Fried, Laila Rosiman, Yael Fisher
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: DICER mutation is a known tumor driver involved in pleuropulmonary blastoma ,renal tumors, masses in the thyroid and ovary and multiple other manifestations. Brain tumors are considered to be a rare manifestation of germline DICER mutation. Currently, brain imaging is not included in the standard follow up of patients with DICER germline mutation, and data re the prevalence of somatic DICER mutations in brain tumors is limited. AIMs: evaluation of prevalence of DICER mutations in a large cohort of rare/relapsed brain tumors. METHODS: over the last year all patients with tumors lacking curative standard therapy in Israel were sent for next generation sequencing,. Molecular evaluation was done using either panel based evaluation (ONCOMINE/Foundation) or whole exome and whole transcriptome (INFORM consortium). Epidemiological data as well as clinical outcome were provided by the treating physician. RESULTS: Between April 2021 and January 2022 one hundred twenty nine samples were sent for molecular analysis, 58 of them were brain tumors. Six patients had DICER associated malignant tumors , 33% of them were brain tumors . One patient with pinealoblastoma was diagnosed with a highly metastatic disease associated with a very grave prognosis. CONCLUSION: brain tumors are an important group among malignant DICER associated tumors. Surveillance may lead to early detection which may be associated with a better outcome.
Predicting true pathologic Gleason grade during active surveillance for prostate cancer: Calibration of the Johns Hopkins ActiveCare Model in five large active surveillance cohorts
Authors: C. Pavlovich, D. Nieboer, M. Mamawala, A. Nishimura, P. Landis, K. Macura, J.I. Epstein, J. Helleman, B. Trock
Journal: European Urology (2022)